RESUMEN
Chronic Myeloid Leukemia is a neoplastic disease characterized by the abnormal expansion of hematopoietic cells with compromised functions. Leukemic cells often display a multidrug resistance phenotype, enabling them to evade a number of structurally unrelated cytotoxic compounds. One of those mechanisms relies on the high expression of efflux transporters, such as the ABC proteins, whose activity depends on the hydrolysis of ATP to reduce intracellular drug accumulation. In the present work, we employed a well-known erythroleukemia cell line, K562, and a multidrug resistant derivative cell, FEPS, to evaluate how hexokinase II, a key regulator for the rate-limiting step glycolysis, contributes to the establishment of the multidrug resistance phenotype. We found that multidrug resistant cells primarily resort to glycolysis to generate ATP. Clotrimazole reduced the expression of mitochondrial hexokinase II, which destabilized bioenergetic parameters such as reactive oxygen species production, ATP, and glutathione levels on multidrug resistant cells. This impaired the activity of ABCC1, leading to increased drug accumulation and cell death. In summary, we propose that decoupling of hexokinase II from the mitochondria emerges as a promising strategy to generate collateral sensitivity and aid in the management of chronic myeloid leukemia in chemotherapy-refractory patients.
RESUMEN
RESUMO Os carcinomas de células renais (CCRs) são o sétimo tipo histológico de câncer mais comum no mundo ocidental e vêm apresentando uma tendência mantida de aumento em sua prevalência. O presente estudo teve por objetivo analisar dados clínicos, demográficos e anatomopatológicos, a partir de prontuários de pacientes diagnosticados com câncer renal, em um centro de referência de oncologia do norte gaúcho. Métodos: Trata-se de pesquisa transversal, realizada com 105 pacientes submetidos a nefrectomias, no período de janeiro de 2013 a setembro de 2018. Resultados: A nefrectomia radical foi realizada em 84,5% de amostras e o anatomopatológico indicou o carcinoma de células claras em 74,1%. Em relação ao sexo, a maioria foi do sexo masculino 64,10% e a idade média foi de 59.9 anos (DP+-11,5), variando de 31 a 81 anos. Quanto aos sintomas, 18% apresentaram a hematúria, em 13,5% dor em flanco, em 10% dor abdominal, e 6,8% dor lombar. Conclusões: O estudo mostrou que o padrão clinico-epidemiológico da neoplasia no hospital estudado está em concordância com a literatura. PALAVRAS-CHAVE: Neoplasias renais, perfil de saúde, neoplasias por tipo histológico
Renal cell carcinomas (RCCs) are the seventh most common histological type of cancer in the Western world and have been showing a sustained upward trend in their prevalence. This study aimed to analyze clinical, demographic and anatomopathological data from medical records of patients diagnosed with kidney cancer, in an oncology reference center in the north of Rio Grande do Sul. Methods: This is a cross-sectional study, carried out with 105 patients undergoing nephrectomies, from January 2013 to September 2018. Results: Radical nephrectomy was performed in 84.5% of samples and the pathological examination indicated clear cell carcinoma in 74.1%. Regarding gender, the majority were male 64.10% and the mean age was 59.9 years (SD+-11.5), ranging from 31 to 81 years. As for symptoms, 18% had hematuria, 13.5% had flank pain, 10% had abdominal pain, and 6.8% had low back pain. Conclusions: The study showed that the clinical-epidemiological pattern of RCC in the studied hospital is in agreement with the literature. KEYWORDS: Kidney neoplasms, health profile, neoplasms by histological type
RESUMEN
[This corrects the article DOI: 10.3389/fonc.2019.01430.].
RESUMEN
Tumor cells exhibit rewired metabolism. We carried out comparative analyses attempting to investigate whether metabolic reprograming could be measured by isothermal microcalorimetry. Intact metastatic cell lines of tongue cell carcinoma, human and murine melanoma, lung, and breast tumors consistently released more heat than non-metastatic cells or cells displaying lower metastatic potential. In tongue squamous carcinoma cells mitochondrial enriched extract reproduced the heat release pattern of intact cells. Cytochalasin D, an actin filament inhibitor, and suppression of metastasis marker Melanoma associated gene 10 (MAGEA10) decreased heat release. Uncoupling protein 2 was highly expressed in metastatic cells, but not in non-metastatic cells. Carnitine palmitoyl transferase-1 inhibitor, Etomoxir strongly inhibited heat release by metastatic cells, thus linking lipid metabolism to thermogenesis. We propose that heat release may be a quantifiable trait of the metastatic process.
